Research Focus of the Laboratory:
Our research is focused on the mechanosensory hair cells that are the receptor cells of hearing and balance. Specifically we are interested in the molecular signals that regulate the survival, homeostasis, and death of these cells. Mammalian hair cells are terminally differentiated and are not regenerated when they are lost. Therefore human hair cells must survive and function for up to a century (or longer) in order to transduce sound and head movement into the neural signals of hearing and balance throughout a normal lifespan. During this lengthy period of time, the hair cell may encounter multiple potentially-toxic stimuli, including exposure to excessive sound and/or exposure to therapeutic drugs with ototoxic side effects. Hair cells must be able to respond rapidly and effectively to these and other potentially-cytotoxic stimuli if they are to survive and continue to function.
We are examining the signals that mediate the survival and death of hair cells under stress. We are currently studying the role of stress-induced proteins called heat shock proteins (HSPs) in protecting against hair cell death. Our studies utilize an in vitro preparation of the adult mouse utricle (a balance organ in the inner ear), which is the best-characterized model system for in vitro studies of mature mammalian hair cells. Using this preparation, we have shown that HSPs inhibit hair cell death caused by both major classes of ototoxic drugs, namely the aminoglycoside antibiotics and the antineoplastic agent cisplatin. In addition, we have shown that mice that constitutively express HSP70 are resistant to hearing loss and cochlear hair cell death caused by systemic aminoglycoside exposure. Our studies indicate that HSP induction is a critical stress response in the inner ear that can promote survival of hair cells exposed to major stressors.
Currently our studies are broadly divided into two groups: 1) those aimed at understanding the molecular mechanisms underlying the protective effects of HSPs and 2) those aimed at translating our findings into clinical therapies to prevent hearing loss caused by exposure to ototoxic drugs. This work is supported by NIH/NIDCD.